Project

Back to overview

Study of the molecular mechanisms of Yersinia and Capnocytophaga infections

English title Study of the molecular mechanisms of Yersinia and Capnocytophaga infections
Applicant Cornelis Guy Richard
Number 128659
Funding scheme Project funding (Div. I-III)
Research institution Abteilung Mikrobiologie Biozentrum Universität Basel
Institution of higher education University of Basel - BS
Main discipline Experimental Microbiology
Start/End 01.01.2010 - 30.09.2012
Approved amount 620'000.00
Show all

All Disciplines (2)

Discipline
Experimental Microbiology
Medical Microbiology

Keywords (7)

microbial pathogenesis; infection; yersinia; protein translocation; type-III secretion; capnocytophaga; dog bites

Lay Summary (English)

Lead
Lay summary
Our research aims at understanding the molecular aspects of bacterial infections and, in particular how bacterial pathogens neutralize macrophages, sentinels of the innate immune system. The goal is to shape new concepts and identify new targets for future prevention and treatment of infectious diseases.Many bacteria, including Yersinia, the agents of plague and human enterocolitis, have the capacity to inject "effector" proteins into the cytosol of animal, plant or insect cells, a process called "type-III secretion" (T3S). The effectors disarm or reprogram the target cell by sabotaging or hijacking the cellular signaling network. The T3S apparatus, called injectisome, is a complex nanosyringe made of more than 25 different proteins. It consists of a transmembrane basal body and a ca 60-nm long needle protruding from the surface. The injectisome is one of the most complex bacterial nanomachines known. It represents a remarkable model of bio nanomachines and it is also an excellent target for vaccines or drugs. For instance, we have discovered that the best protective antigen against plague forms the structure at the needle tip. Presently, we focus on how the 25 different proteins of the Yersinia injectisome assemble in an ordered way and how this machine controls its needle length.We also study Capnocytophaga canimorsus, a bacterium commonly found in dog's mouths and responsible for fatal septicemia or meningitis in humans after dog bites or licks. Our goal is to understand these dramatic cases and to find ways to prevent them. In addition, this study of C. canimorsus shed light on the relation between commensals and their host and illustrates how thin is the line separating a commensal from a pathogen. We have established that these bacteria are not detected by macrophages and even that some strains block the macrophage proinflammatory signalling pathway. We try now to understand the molecular mechanisms underlying this immunosuppression and to see whether this mechanism is present in every C. canimorsus isolate or only in very few strains.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Assembly of the Yersinia injectisome: the missing pieces.
Diepold Andreas, Wiesand Ulrich, Amstutz Marlise, Cornelis Guy R (2012), Assembly of the Yersinia injectisome: the missing pieces., in Molecular microbiology, 85(5), 878-92.
The lipopolysaccharide from Capnocytophaga canimorsus reveals an unexpected role of the core-oligosaccharide in MD-2 binding.
Ittig Simon, Lindner Buko, Stenta Marco, Manfredi Pablo, Zdorovenko Evelina, Knirel Yuriy A, dal Peraro Matteo, Cornelis Guy R, Zähringer Ulrich (2012), The lipopolysaccharide from Capnocytophaga canimorsus reveals an unexpected role of the core-oligosaccharide in MD-2 binding., in PLoS pathogens, 8(5), 1002667-1002667.
Translocators YopB and YopD from Yersinia enterocolitica form a multimeric integral membrane complex in eukaryotic cell membranes.
Montagner Caroline, Arquint Christian, Cornelis Guy R (2011), Translocators YopB and YopD from Yersinia enterocolitica form a multimeric integral membrane complex in eukaryotic cell membranes., in Journal of bacteriology, 193(24), 6923-8.
Complete genome sequence of the dog commensal and human pathogen Capnocytophaga canimorsus strain 5.
Manfredi Pablo, Pagni Marco, Cornelis Guy R (2011), Complete genome sequence of the dog commensal and human pathogen Capnocytophaga canimorsus strain 5., in Journal of bacteriology, 193(19), 5558-9.
The assembly of the export apparatus (YscR,S,T,U,V) of the Yersinia type III secretion apparatus occurs independently of other structural components and involves the formation of an YscV oligomer.
Diepold Andreas, Wiesand Ulrich, Cornelis Guy R (2011), The assembly of the export apparatus (YscR,S,T,U,V) of the Yersinia type III secretion apparatus occurs independently of other structural components and involves the formation of an YscV oligomer., in Molecular microbiology, 82(2), 502-14.
The genome and surface proteome of Capnocytophaga canimorsus reveal a key role of glycan foraging systems in host glycoproteins deglycosylation.
Manfredi Pablo, Renzi Francesco, Mally Manuela, Sauteur Loïc, Schmaler Mathias, Moes Suzette, Jenö Paul, Cornelis Guy R (2011), The genome and surface proteome of Capnocytophaga canimorsus reveal a key role of glycan foraging systems in host glycoproteins deglycosylation., in Molecular microbiology, 81(4), 1050-60.
The N-glycan glycoprotein deglycosylation complex (Gpd) from Capnocytophaga canimorsus deglycosylates human IgG.
Renzi Francesco, Manfredi Pablo, Mally Manuela, Moes Suzette, Jenö Paul, Cornelis Guy R (2011), The N-glycan glycoprotein deglycosylation complex (Gpd) from Capnocytophaga canimorsus deglycosylates human IgG., in PLoS pathogens, 7(6), 1002118-1002118.

Associated projects

Number Title Start Funding scheme
113333 Study of the molecular mechanisms of Yersinia and Capnocytophaga infections 01.01.2007 Project funding (Div. I-III)

-